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<p>Nearly half of the genome of humans and other mammals consists of transposable elements (TEs). Recent advancements in sequencing technologies have revealed that TEs have important regulatory functions, echoing Barbara McClintock’s 1950s vision of TEs as ‘controlling elements’. Nevertheless, TEs can still interfere with gene expression and are linked to various human diseases. In this Review, we first discuss the multilayered transcriptional and post-transcriptional defence mechanisms that repress TE activity, and examine how they regulate endogenous gene expression. We then discuss recent studies showing that TEs can escape these repression mechanisms and unexpectedly become a vital part of animal development. Finally, we explore findings on TE derepression in cancer and neurological diseases, and emerging therapeutic strategies that exploit TE derepression, such as immunotherapies that target TE-derived tumour-specific antigens.</p>

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Transcriptional and post-transcriptional regulation of transposable elements and their roles in development and disease

  • 期刊论文

  • 发表日期：

    2025年6月30日

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  • İbrahim Avşar Ilık,
  • Xu Yang,
  • ZZ Zhao Zhang,
  • Tuğçe Aktaş

摘要

Nearly half of the genome of humans and other mammals consists of transposable elements (TEs). Recent advancements in sequencing technologies have revealed that TEs have important regulatory functions, echoing Barbara McClintock’s 1950s vision of TEs as ‘controlling elements’. Nevertheless, TEs can still interfere with gene expression and are linked to various human diseases. In this Review, we first discuss the multilayered transcriptional and post-transcriptional defence mechanisms that repress TE activity, and examine how they regulate endogenous gene expression. We then discuss recent studies showing that TEs can escape these repression mechanisms and unexpectedly become a vital part of animal development. Finally, we explore findings on TE derepression in cancer and neurological diseases, and emerging therapeutic strategies that exploit TE derepression, such as immunotherapies that target TE-derived tumour-specific antigens.